The c-Jun N-terminal protein kinases (JNKs) are a family of serine/threonine protein kinases of the mitogen-activated protein kinase (MAPK) group. JNKs, which are essential regulators of physiological and pathological processes, are involved in several diseases including diabetes, atherosclerosis, stroke, and Parkinson's and Alzheimer's diseases. The JNK family consists of three isoforms; JNK1 and JNK2, which are ubiquitous, and JNK3, which is present primarily in the heart, brain and testis. Differential splicing and exon use yield 10 isoforms of JNK. JNK1 is an important mediator of insulin resistance associated with obesity, but it is also indispensable for the intact cytoarchitecture of the brain. Responds to activation by environmental stress and pro-inflammatory cytokines by phosphorylating a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity. In T-cells, JNK1 and JNK2 are required for polarized differentiation of T-helper cells into Th1 cells. Phosphorylates heat shock factor protein 4 (HSF4). JNK1 isoforms display different binding patterns: β-1 preferentially binds to c-Jun, whereas α-1, α-2, and β-2 have a similar low level of binding to both c-Jun or ATF2. However, there is no correlation between binding and phosphorylation, which is achieved at about the same efficiency by all isoforms.